The pathogenicity of group A streptococci is being studied to gain further insight into the mechanisms of infection and poststreptococcal sequelae. Proposed and continuing projects include the following: 1. The structure of M proteins, the protective antigens of group A streptococci, is being studied. New techniques such as detergent extraction are being investigated for obtaining M proteins for further purification. Structural analyses are being carried on to determine the composition and amino acid sequence of M proteins from "rheumatogenic" and "nephritogenic" streptococci; 2. An in vitro model for the mechanism of rheumatic heart disease is being developed with cultured cardiac myofibers are target cells for lymphocytes "sensitized" to various streptococcal antigens in order to determine the role of cell-mediated immunity in rheumatic heart disease. Spleen lymphocytes from guinea pigs sensitized with protoplast membranes are cytotoxic for guinea pig embryonic cardiac myofibers in culture. Lymphocytes from guinea pigs sensitized to group C streptococcal antigens or membranes show signficantly lower cytotoxic properties. Cultured skeletal muscle or liver cells as controls were not susceptible targets for group A sensitized lymphocytes. Data thus far implicate T-cell rich populations (rather than B cells) as the aggressor cell; 3. Synthetic lipid bilayers (liposomes) are being prepared with solubilized membrane fractions from streptococcal protoplasts and from sarcolemma of human myocardium. The antigenic specificity of these vesicles will be assessed by release of internal marker with sera known to cross-react with heart and streptococci. Rheumatic fever sera will also be studied in this system. BIBLIOGRAPHIC REFERENCES: Polly, S.M., Waldman, R.H., High, P., Wittner, M.K., Dorfman, A., and Fox, E.N. 1975. Protective studies with a group A streptococcal M protein vaccine. II. Challenge of volunteers following local immunization in the upper respiratory tract. J. Infect. Diseases, 131, 217-224. Wittner, M.K. 1976. Antigenicity of the M proteins of group A hemolytic streptococci. VI. Further evidence for shared determinants among serotypes. Infect. Immun. 13, 634-642.